A neonate presents with lethargy, vomiting, hyperammonemia (NH3 1200 µmol/L), respiratory alkalosis, and plasma citrulline undetectable. Urine orotic acid is elevated. Which enzyme deficiency best explains this presentation?

• A Carbamoyl phosphate synthetase I (CPS I)
• B Argininosuccinate synthetase (citrullinemia type I)
• C Ornithine transcarbamylase (OTC) ✓
• D Arginase

Explanation

OTC deficiency (X-linked) is the most common urea cycle defect. Carbamoyl phosphate accumulates and spills into the cytoplasm, driving excess orotic acid synthesis via the pyrimidine pathway — hence elevated urine orotic acid. Plasma citrulline is low/absent because OTC (which condenses ornithine + carbamoyl phosphate → citrulline in the mitochondria) is absent. CPS I deficiency also produces near-zero citrulline but orotic acid is normal or low because carbamoyl phosphate does not accumulate in the cytoplasm. Citrullinemia shows high citrulline.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.